Definition

A monoclonal antibody directed against human killer cell immunoglobulin-like receptor 3DL3 (killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 3; KIR3DL3), an inhibitory receptor for human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2; B7 homolog 7; B7-H7), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, anti-KIR3DL3 monoclonal antibody NPX267 binds to KIR3DL3 expressed on T cells and natural killer (NK) cells and prevents the binding of KIR3DL3 to HHLA2 expressed on tumor cells. This abrogates the KIR3DL3/HHLA2-mediated inhibition of T-cell and NK-cell activation in the tumor microenvironment (TME), which may lead to enhanced cytotoxic T-lymphocyte (CTL)-mediated immune response and NK cell cytotoxicity against cancer cells. HHLA2, a member of the B7 family of immune modulators, is upregulated in a variety of tumor cell types. The KIR3DL3-HHLA2 pathway is an immunosuppressive pathway and a negative regulator of T-cell and NK-cell activation.